title: Impact of portal branch ligation on tissue regeneration, microcirculatory response and microarchitecture in portal blood-deprived and undeprived liver tissue.
abstract: Partial ligation of portal branches leads to atrophy of the deprived lobes and hypertrophy of the intact lobes. In this study we investigated the microcirculatory response and their consequences on tissue regeneration after left-sided portal branch ligation (PBL) in Sprague-Dawley rats. At day 1 and 3 after PBL the hepatic microcirculation was assessed by intravital microscopy (IVM). In addition histological, immunohistochemical and biochemical techniques were used to determine alterations of hepatic microarchitecture. IVM analysis of the microcirculation of the ligated hepatic lobes revealed significant alterations with a reduction in sinusoidal perfusion rate, a decrease of red blood cell velocity, an increase of sinusoidal diameter and a marked reduction in shear stress at days 1 and 3 after PBL. On the contrary, the non-ligated lobes presented with higher blood flow velocities, marked sinusoidal vasoconstriction and thus, shear stress elevation. In consequence, ligated liver lobes exhibited marked cell apoptosis and necrosis, being accompanied by massive intrahepatic leukocyte accumulation and a ~30% weight loss. The non-ligated liver tissue showed marked PCNA expression and thereby completely compensated weight loss. Beside full restoration of liver mass, sinusoidal blood flow was comparable in ligated and non-ligated lobes as well as in sham-treated controls. This study shows that the liver aims at constant tissue mass and blood flow, most probably for maintenance of adequate clearance function. In addition, it supports the hypothesis that shear stress plays a pivotal role in triggering liver hypertrophy in the non-ligated lobes.
authors.affiliation: Department of General, Vascular, Thoracic and Transplantation Surgery, University of Rostock, 18057 Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gock
authors.forename: Christian
authors.initials: C
authors.lastname: Eipel
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebacher
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy / Q000473:pathology; D001783:Blood Flow Velocity / Q000502:physiology; D001835:Body Weight; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000166:cytology; D008026:Ligation; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D008102:Liver Circulation / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008833:Microcirculation / Q000502:physiology*; D009336:Necrosis / Q000473:pathology; D009929:Organ Size; D011169:Portal Vein / Q000601:surgery*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat